Sepsis (severe bloodstream borne infection) and the resultant multiorgan failure it induces are the number one cause of death in the surgical intensive care unit and a leading cause of morbidity and mortality in the neonatal and medical intensive care unit. The Center for Disease Control has estimated that approximately 400,000 people develop endotoxic shock annually. Despite medical advances, the critically-ill patient who develops sepsis and hypotension has a mortality of 40 to 60 percent, levels that have remained unchanged over the past 15 years. A current hypothesis is that disturbances in cellular calcium regulation are responsible for many of the metabolic manifestations of sepsis and may be the driving force behind the development of the multiorgan failure. Calcium functions as a critical intracellular second messenger and regulates many cellular processes such as muscle contractility, glycogen turnover, protein degradation, and vascular smooth muscle tone which are markedly abnormal during sepsis. 19F nuclear magnetic resonance spectroscopy and the 19F NMR active calcium indicator 5FBAPTA provide a unique opportunity to determine the key variable, viz, Cai 2+ in intact perfused organs thereby avoiding changes in cellular calcium which may occur during cell culture or in preparation of isolated cells. The purpose of this investigation is to utilize NMR spectroscopy to determine the nature of the alterations in intracellular calcium under physiologic conditions which exist in vivo during this lethal disorder. The cecal ligation and perforation model sepsis in the rat will be used to induce sepsis. At 36 hours following surgery, 19F NMR spectroscopy and 5FBAPTA will be used to measure [Ca2+]i in the perfused heart and perfused aorta (two organs known to be affected by sepsis) from septic and sham operated rats. Because of recent evidence establishing that [Na+]i is a key determinant of [Ca2+]i, we will also utilize 23 Na NMR spectroscopy to test our hypothesis that increased [Na+]i (acting on the Na+ /Ca2+ exchanger) is the primary mechanism responsible for increased [Ca2+]i. The results from this investigation will impact upon current controversial clinical issues such as the role of calcium supplementation in the hypocalcemic septic patient, and may provide a rationale for the selection of specific calcium channel blocking agents which have been demonstrated to increase survival in animal models of sepsis/endotoxemia.